The first step in establishment of infectious diarrheal disease is the attachment of the invading pathogenic bacteria to the host tissue. In the case of enterotoxigenic Escherichia coli (ETEC), this is mediated by colonization factor antigens which constitute the major subunit of proteinaceous surface structures on the bacteria (pili or fimbriae). CFA/I, CFA/II and E8775 have been identified so far in human ETEC strains. CFA/II is composed of three separate antigens, called CSl, 2, and 3. These antigens are plasmid encoded, but their expression is regulated by the host and expression of CSl and CS2 is mutually exclusive. We propose to apply molecular techniques to the study of CFA/II antigens to learn about host regulation of plasmid-encoded functions. This work should lead to the understanding of the structure, assembly, genetic control and function of CS2 pili. We hope that the information gleaned will lead to a strategy for the development of a vaccine to protect against human ETEC strains or possibly to an adhesin analog therapy.